Abstract
The diastolic and systolic dysfunction in the failing heart appear to be related to the altered Ca2+ handling of the cardiac myocyte. Disturbed Ca2+ handling might also affect influx and efflux of other ions, including Na+. In this context, the cardiac sarcolemmal Na+/Ca2+ exchanger represents an important exchange mechanism of Ca2+ versus Na+ transport across the sarcolemma. Expression and function of cardiac Na+/Ca2+ exchanger is highest in newborn rats and declines gradually in postnatal development. In pressure overload-induced hypertrophy, expression of cardiac Na+/Ca2+ exchanger is increased and translated into increased Na+/Ca2+ exchanger activity similar to the early phase of postnatal development in the rat. This suggests a common underlying mechanism in the control of Na+/ Ca2+ exchanger expression in the immature and the hypertrophied myocardium. Similar to experimental-induced hypertrophy, mRNA, protein and activity of Na+/Ca2+ exchanger is increased in the failing human heart suggesting an increase in the number of functional exchanger molecules rather than an enhanced exchange rate by preexisting exchanger molecules. The potential functional implications of an increased cardiac Na+/Ca2+ exchanger activity in human heart failure may be limitation of diastolic intracellular Ca2+ overload. However, this may increase the arrhythmogenic potential of the failing heart, since additional Na+ influx via Na+/Ca2+ exchanger may affect the membrane potential.
Similar content being viewed by others
References
Arai M, Matsui H, Periasamy M (1994) Sarcoplasmic reticulum gene expression in cardiac hypertrophy and heart failure. Circ Res 74: 555–564
Artman M (1992) Sarcolemmal Na+−Ca2+ exchange activity and exchanger immunoreactivity in developing rabbit hearts. Am J Physiol 263: H1506-H1513
Bers DM, Bridge JHB (1989) Relaxation of rabbit ventricular muscle by Na−Ca exchange and sarcoplasmic reticulum calcium pump. Cire Res 65: 334–342
Bers DM, Lederer WJ, Berlin JR (1990) Intracellular Ca transients in rat cardiac myocytes: role of Na−Ca exchange in excitation-contraction coupling. Am J Physiol 258: C944-C954
Bers DM, Bassani JW, Bassani RA (1993) Competition and redistribution among calcium transport systems in rabbit cardiac myocytes. Cardiovasc Res 27: 1772–1777
Bing OHL, Brooks WW, Conrad CH, Sen S, Perreault CL, Morgan JP (1991) Intracellular calcium transients in myocardium from spontaneously hypertensive rats during the transition to heart failure. Circ Res 68: 1390–1400
Boerth, SR, Zimmer DB, Artman M (1994) Steady-state mRNA levels of the sarcolemmal Na+−Ca2+ exchanger peak near birth in developing rabbit and rat hearts. Circ Res 74: 354–359
Chien KR, Zhu H, Knowlton KU, Miller Hance W, Van Bilsen M, O'Brien TX, Evans SM (1993) TRanscriptional regulation during cardiac growth and developmen. Annu Rev Physiol 55: 77–95
Fabiato A (1982) Calcium release in skinned cardiac cells: variation with species, tissues, and development. Fed Proc 41: 2238–2244
Fisher DJ, Tate CA, Philips S (1992) Developmental regulation of the sarcoplasmic reticulum calcium pump in the rabbit heart. Pediatr Res 31: 474–479
Gwathmey JK, Copelas L, MacKinnon R, Schoen FJ, Feldman MD, Grossman W, Morgan JP (1987) Abnormal intracellular calcium handling in myocardium from patients with end-stage heart failure. Circ Res 61: 70–76
Hanf R, Dubraix I, Marotte F, Lelievre LG (1988) Rat cardiac hypertrophy. Altered sodium-calcium exchange activity in sarcolemmal vesicles. FEBS Letters 236: 145–149
Hasenfuss G, Mulieri LA, Leavitt BJ, Allen PD, Haeberle JR, Alpert NR (1992) Alteration of contractile function and excitation-contraction coupling in dilated cardiomyopathy. Circ Res 70: 1225–1232
Hasenfuss G, Reinecke H, Studer R, Meyer M, Pieske B, Holtz J, Holubarsch C, Posival H, Just H, Drexler H (1994) Relation between myocardial function and expression of sarcoplasmic reticulum, Ca2+-ATPase in failing and nonfailing human myocardium. Circ Res 75: 434–442
Hatem SN, Sham JSK, Morad M (1994) Enhanced Na+−Ca2+ exchange activity in cardiomyopathic syrian hamster. Circ Res 74: 253–261
Kent RL, Rozich JD, McCollam PL, McDermott DE, Thacker UF, Menick DR, McDermott PJ, Cooper IV G (1993) Rapid expression of the Na+−Ca2+ exchanger in response to cardiac pressure overload. Am J Physiol 265: H1024-H1029
Klitzner TS (1991) Maturational changes in excitation-contraction coupling in mammalian myocardium. J Am Coll Cardiol 17: 218–225
Komuro I, Kurabayashi M, Shibazaki Y, Takaku F, Yazaki, Y (1989) Molecular cloning and characterization of a Ca2++ Mg2+-dependent adenosine triphosphatase from rat cardiac sarcoplasmic reticulum. Regulation of its expression by pressure overload and developmental stage. J Clin Invest 83: 1102–1108
Leblanc N, Hume JR (1990) Sodium current-induced release of calcium from cardiac sarcoplasmatic reticulum. Science 248: 372–376
Limas CJ, Olivari M, Goldenberg IF, Levine TB, Benditt DG, Simon A (1987) Calcium uptake by cardiac sarcoplasmic reticulum in human dilated cardiomyopathy. Cardiovasc Res 21: 601–605
Lompré A-M, Lambert F, Lakatta EG, Schwartz K (1991) Expression of sarcoplasmic reticulum Ca2+-ATPase and calsequestrin genes in rat heart during ontogenic development and aging. Circ Res 69: 1380–1388
Mercadier J-J, Lompré A-M, Duc P, Boheler KR, Fraysse JB, Wisnewsky C, Allen PD, Komajda M, Schwartz K (1990) Altered sarcoplasmic reticulum Ca2+-ATPase gene expression in human ventricle during end-stage heart fanure. J Clin Invest 85: 305–309
Morgan JP, Erny RE, Allen PD, Grossman W, Gwathmey JK (1990) Abnormal intracellular calcium handling: a major cause of systolic and diastolic dysfunction in ventricular myocardium from patients with heart failure. Circulation 61 Suppl III: III21–32
Morgan JP (1991) Mechanisms of disease — abnormal intracellular modulation of calcium as a major cause of cardiac contractile dysfunction. New Engl J Med 325: 625–632
Nakanishi H, Makino N, Hata T, Mataun H, Yano K, Yanaga T (1989) Sarcolemmal Ca2+ transport activities in cardiac hypertrophy caused by pressure overload. Am J Physiol 257: H349-H356
Negretti N, O'Neill SC, Eisner DA (1993) The relative contributions of different intracellular and sarcolemmal systems to relaxation in rat ventrice myocytes. Cardiovasc Res 27: 1826–1830
Ostádalová I, Kolár F, Ostádal B, Rohlicek V, Rohlicek J, Prochazka J (1993) Early postnatal development of contractile performance and responsiveness to Ca2+, verapamil and ryanodine in the isolated rat heart. J Mol Cell Cardiol 25: 733–740
Reinecke H, Studer R, Vetter R, Holtz J, Drexler H (1995) Cardiac Na+/Ca2+ exchange activity in patients with endstage heart failure. Cardiovasc Res, in press
Seguchi M, Harding JA, Jarmakani JM (1986) Developmental change in the function of sarcoplasmic reticulum. J Mol Cell Cardiol 18: 189–195
Studer R, Reinecke H, Vetter R, Holtz J, Drexler H (1993) Enhanced expression and function of the Na+/Ca2+ exchanger in rat ventricular trophy and in myocardium of neonatal rats. (Abstract) Circulation 88 Suppl VI 86
Studer R, Reinecke H, Bilger, J, Eschenhagen T, Böhm M, Hasenfuß G, Just H, Holtz J, Drexler H (1994) Gene expression of the cardiac Na+−Ca2+ exchanger in end-stage human heart failure. Circ Res 75: 443–453
Tanaka H, Shigenobu K (1989) Effect of ryanodine on neonatal and adult rat heart: developmental increase in sarcoplasmic reticulum function. J Mol Cell Cardiol 21: 1305–1313
Vetter R, Kemsies C, Schulze W (1987) Sarcolemmal Na+−Ca2+ exchange and sarcoplasmic reticulum Ca2+ uptake in several cardiac preparations. Biomed Biochim Acta 46: S375-S381
Vetter R, Studer R, Reinecke H, Kolár F, Ostádalová I, Drexler H (1995) Reciprocal changes in the post-natal expression of the sarcolemmal Na+−Ca2+ exchanger and SERCA2 in rat heart. J Mol Cell Cardiol 27: 1689–1701
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Studer, R., Reinecke, H., Vetter, R. et al. Expression and function of the cardiac Na+/Ca2+ exchanger in postnatal development of the rat, in experimentaliduced cardiac hypertrophy and in the failing human heart. Basic Res Cardiol 92 (Suppl 1), 53–58 (1997). https://doi.org/10.1007/BF00794068
Issue Date:
DOI: https://doi.org/10.1007/BF00794068